Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 19104, USA.
McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Sci Transl Med. 2018 Nov 21;10(468). doi: 10.1126/scitranslmed.aau0670.
Tissue engineering holds great promise for the treatment of advanced intervertebral disc degeneration. However, assessment of in vivo integration and mechanical function of tissue-engineered disc replacements over the long term, in large animal models, will be necessary to advance clinical translation. To that end, we developed tissue-engineered, endplate-modified disc-like angle ply structures (eDAPS) sized for the rat caudal and goat cervical spines that recapitulate the hierarchical structure of the native disc. Here, we demonstrate functional maturation and integration of these eDAPS in a rat caudal disc replacement model, with compressive mechanical properties reaching native values after 20 weeks in vivo and evidence of functional integration under physiological loads. To further this therapy toward clinical translation, we implanted eDAPS sized for the human cervical disc space in a goat cervical disc replacement model. Our results demonstrate maintenance of eDAPS composition and structure up to 8 weeks in vivo in the goat cervical disc space and maturation of compressive mechanical properties to match native levels. These results demonstrate the translational feasibility of disc replacement with a tissue-engineered construct for the treatment of advanced disc degeneration.
组织工程学为治疗晚期椎间盘退变提供了巨大的潜力。然而,为了推进临床转化,有必要在大型动物模型中对长期的、体内组织工程椎间盘替代物的整合和机械功能进行评估。为此,我们开发了适合大鼠尾椎和山羊颈椎的组织工程化、终板修饰的角层状盘状结构(eDAPS),其大小与天然椎间盘的层次结构相匹配。在这里,我们在大鼠尾椎间盘置换模型中展示了这些 eDAPS 的功能成熟和整合,在体内 20 周后压缩力学性能达到天然水平,并在生理负荷下显示出功能整合的证据。为了将这种治疗方法推向临床转化,我们在山羊颈椎椎间盘置换模型中植入了适合人类颈椎椎间盘间隙的 eDAPS。我们的结果表明,在山羊颈椎椎间盘间隙中,eDAPS 的组成和结构在体内可维持 8 周,压缩力学性能可成熟到与天然水平相匹配。这些结果表明,使用组织工程构建物进行椎间盘置换治疗晚期椎间盘退变具有转化的可行性。